| Objective:It is usually considered that liver injury is mediated by host immune responses in HBV infection, particularly in patients with chronic hepatitis B (CHB). In the past, HBV-specific CTLs are regarded as the main effectors for liver injury, but little is known about the role of innate immune cells in these processes. In this study, we investigated the relationship between the TRAIL expression by NK cells and the liver damage severity in patients with HBeAg+ chronic hepatitis B.Methods:Peripheral blood was obtained from 54 HBeAg+CHB patients with ALT elevation (IA),16 patients with immune tolerant (IT) and 36 healthy controls (HC). Next, peripheral blood mononuclear cells (PBMCs) were collected by Ficoll-Hypaque method. TRAIL expression by NK cells was examined by using flow cytometry. We also studied the cytoxic mechanisms by which NK cells killed HepG2 or HepG2.2.15 cells. Finally, we analyzed the effect of IFN-a on TRAIL expression both in vitro and in vivo.Results:The frequency of peripheral CD56bright NK subsets in patients with HBeAg+ chronic hepatitis B was significantly increased compared with patients in IT and HC groups (p=0.01 and 0.007). TRAIL expression by peripheral NK cells, especially CD56bright NK subsets, was also significantly increased. More importantly, increased CD56bright frequency and TRAIL expression were found to positively correlate with increased ALT level(R=0.46,p＜0.001; R=0.52; p=0.03). Cytoxicity of NK cells against HepG2 or HepG2.2.15 cells increased more significantly in IA patients than IT or HC groups(p<0.05). Blocking TRAIL pathway was found to reduce target cell death. Finally, our results showed that IFN-a treatment increase TRAIL expression on NK cells both in vitro and in vivo.Conclusions:Our findings indicated that TRAIL up-regulation on NK cells may be associated with liver injury in patients with HBeAg+chronic hepatitis B. IFN-a could increase TRAIL expressing NK cells in vivo, which may boost the immune function of NK cells.
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